This proposal titled """"""""Combination Growth Factor Antagonist/Chemotherapy in PCa"""""""" is a request for a NCI Mentored Patient-Oriented Research Career Development Award (K23). The candidate is interested in the study of growth factor receptor tyrosine kinases (RTKs) and their relevance in prostate cancer. There is emerging evidence that certain RTKs, specifically platelet derived growth factor receptor (PDGFr) and epidermal growth factor receptor (EGFr) have a role in the growth advanced hormone independent prostate cancer. Small molecules which inhibit the phosphorylation of these receptors appear to have a cytostatic effect on neoplastic cell growth including in prostate cancer cells. The candidate is currently enrolled in a formal clinical investigation training program designed to educate investigators in early drug development. The proposed project is designed to test the hypothesis that combination therapy with PDGFr or EGFr antagonists with cytotoxic chemotherapy can be synergistic in the treatment of advanced prostate cancer. This proposal will provide experience in developing a therapeutic approach in the preclinical model and translating these findings into a clinical trial to evaluate their role in the treatment of human prostate cancer. The first phase will determine the in vivo molecular interaction of these agents with DNA damaging chemotherapy. These will then be tested in prostate cancer xenografts and in the orthotopic model. The third phase will evaluate the optimal combinations in human clinical trials with pharmacodynamic endpoints. This research project is designed to integrate the preclinical investigation of these novel agents with effective clinical evaluation in order to optimize their development. This will guide the development of the candidate into an independent translational investigator in prostate cancer. The research conducted will expand the current knowledge of the biology of hormone independent prostate cancer and its management.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23CA085436-03
Application #
6522573
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2000-08-01
Project End
2005-07-31
Budget Start
2002-08-16
Budget End
2003-01-31
Support Year
3
Fiscal Year
2002
Total Cost
$61,469
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Ko, Yoo-Joung; Devi, Gayathri R; London, Carla A et al. (2004) Androgen receptor down-regulation in prostate cancer with phosphorodiamidate morpholino antisense oligomers. J Urol 172:1140-4
Balk, Steven P; Ko, Yoo-Joung; Bubley, Glenn J (2003) Biology of prostate-specific antigen. J Clin Oncol 21:383-91